Advances in Studies of P-Glycoprotein and Its Expression Regulators
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- Yano Kentaro
- Faculty of Pharmacy, Takasaki University of Health and Welfare
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- Tomono Takumi
- Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare
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- Ogihara Takuo
- Faculty of Pharmacy, Takasaki University of Health and Welfare Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare
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説明
<p>This review deals with recent advances in studies on P-glycoprotein (P-gp) and its expression regulators, focusing especially on our own research. Firstly, we describe findings demonstrating that the distribution of P-gp along the small intestine is heterogeneous, which explains why orally administered P-gp substrate drugs often show bimodal changes of plasma concentration. Secondly, we discuss the post-translational regulation of P-gp localization and function by the scaffold proteins ezrin, radixin and moesin (ERM proteins), together with recent reports indicating that tissue-specific differences in regulation by ERM proteins in normal tissues might be retained in corresponding cancerous tissues. Thirdly, we review evidence that P-gp activity is enhanced in the process of epithelial-to-mesenchymal transition (EMT), which is associated with cancer progression, without any increase in expression of P-gp mRNA. Finally, we describe two examples in which P-gp critically influences the brain distribution of drugs, i.e., oseltamivir, where low levels of P-gp associated with early development allow oseltamivir to enter the brain, potentially resulting in neuropsychiatric side effects in children, and cilnidipine, where impairment of P-gp function in ischemia allows cilnidipine to enter the ischemic brain, where it exerts a neuroprotective action.</p>
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 41 (1), 11-19, 2018
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679611132672
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- NII論文ID
- 130006301301
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 028739226
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- PubMed
- 29311472
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可